Infection and Vaccine Induced Spike Antibody Responses Against SARS-CoV-2 Variants of Concern in COVID-19-Naïve Children and Adults.

Pillay, A; Yeola, A; Tea, F; Denkova, M; Houston, S; Burrell, R; Merheb, V; Lee, FXZ; Lopez, JA; Moran, L; Jadhav, A; Sterling, K; Lai, CL; Vitagliano, TL; Aggarwal, A; Catchpoole, D; Wood, N; Phan, TG; Nanan, R; Hsu, P; Turville, SG; Britton, PN; Brilot, F

Infection and Vaccine Induced Spike Antibody Responses Against SARS-CoV-2 Variants of Concern in COVID-19-Naïve Children and Adults.

Pillay, A Yeola, A Tea, F Denkova, M Houston, S Burrell, R Merheb, V Lee, FXZ Lopez, JA Moran, L Jadhav, A Sterling, K Lai, CL Vitagliano, TL Aggarwal, A Catchpoole, D

Wood, N Phan, TG Nanan, R Hsu, P Turville, SG Britton, PN Brilot, F

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Publisher:: SPRINGER/PLENUM PUBLISHERS
Publication Type:: Journal Article
Citation:: J Clin Immunol, 2023, 43, (8), pp. 1706-1723
Issue Date:: 2023-11

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Field	Value	Language
dc.contributor.author	Pillay, A
dc.contributor.author	Yeola, A
dc.contributor.author	Tea, F
dc.contributor.author	Denkova, M
dc.contributor.author	Houston, S
dc.contributor.author	Burrell, R
dc.contributor.author	Merheb, V
dc.contributor.author	Lee, FXZ
dc.contributor.author	Lopez, JA
dc.contributor.author	Moran, L
dc.contributor.author	Jadhav, A
dc.contributor.author	Sterling, K
dc.contributor.author	Lai, CL
dc.contributor.author	Vitagliano, TL
dc.contributor.author	Aggarwal, A
dc.contributor.author	Catchpoole, D https://orcid.org/0000-0001-5836-1413
dc.contributor.author	Wood, N
dc.contributor.author	Phan, TG
dc.contributor.author	Nanan, R
dc.contributor.author	Hsu, P
dc.contributor.author	Turville, SG
dc.contributor.author	Britton, PN
dc.contributor.author	Brilot, F
dc.date.accessioned	2024-03-14T04:33:47Z
dc.date.available	2023-06-19
dc.date.available	2024-03-14T04:33:47Z
dc.date.issued	2023-11
dc.identifier.citation	J Clin Immunol, 2023, 43, (8), pp. 1706-1723
dc.identifier.issn	0271-9142
dc.identifier.issn	1573-2592
dc.identifier.uri	http://hdl.handle.net/10453/176705
dc.description.abstract	Although a more efficient adaptive humoral immune response has been proposed to underlie the usually favorable outcome of pediatric COVID-19, the breadth of viral and vaccine cross-reactivity toward the ever-mutating Spike protein among variants of concern (VOCs) has not yet been compared between children and adults. We assessed antibodies to conformational Spike in COVID-19-naïve children and adults vaccinated by BNT162b2 and ChAdOx1, and naturally infected with SARS-CoV-2 Early Clade, Delta, and Omicron. Sera were analyzed against Spike including naturally occurring VOCs Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1, and variants of interest Epsilon, Kappa, Eta, D.2, and artificial mutant Spikes. There was no notable difference between breadth and longevity of antibody against VOCs in children and adults. Vaccinated individuals displayed similar immunoreactivity profiles across variants compared with naturally infected individuals. Delta-infected patients had an enhanced cross-reactivity toward Delta and earlier VOCs compared to patients infected by Early Clade SARS-CoV-2. Although Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1 antibody titers were generated after Omicron infection, cross-reactive binding against Omicron subvariants was reduced across all infection, immunization, and age groups. Some mutations, such as 498R and 501Y, epistatically combined to enhance cross-reactive binding, but could not fully compensate for antibody-evasive mutations within the Omicron subvariants tested. Our results reveal important molecular features central to the generation of high antibody titers and broad immunoreactivity that should be considered in future vaccine design and global serosurveillance in the context of limited vaccine boosters available to the pediatric population.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	SPRINGER/PLENUM PUBLISHERS
dc.relation.ispartof	J Clin Immunol
dc.relation.isbasedon	10.1007/s10875-023-01540-5
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.subject.classification	3204 Immunology
dc.subject.mesh	Child
dc.subject.mesh	Humans
dc.subject.mesh	Adult
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	COVID-19
dc.subject.mesh	Antibody Formation
dc.subject.mesh	BNT162 Vaccine
dc.subject.mesh	Vaccines
dc.subject.mesh	Antibodies
dc.subject.mesh	Humans
dc.subject.mesh	Vaccines
dc.subject.mesh	Antibodies
dc.subject.mesh	Antibody Formation
dc.subject.mesh	Adult
dc.subject.mesh	Child
dc.subject.mesh	COVID-19
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	BNT162 Vaccine
dc.subject.mesh	Child
dc.subject.mesh	Humans
dc.subject.mesh	Adult
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	COVID-19
dc.subject.mesh	Antibody Formation
dc.subject.mesh	BNT162 Vaccine
dc.subject.mesh	Vaccines
dc.subject.mesh	Antibodies
dc.title	Infection and Vaccine Induced Spike Antibody Responses Against SARS-CoV-2 Variants of Concern in COVID-19-Naïve Children and Adults.
dc.type	Journal Article
utslib.citation.volume	43
utslib.location.activity	Netherlands
utslib.for	1107 Immunology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Computer Science
utslib.copyright.status	open_access	*
dc.date.updated	2024-03-14T04:33:42Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	43
utslib.citation.issue	8

Abstract:

Although a more efficient adaptive humoral immune response has been proposed to underlie the usually favorable outcome of pediatric COVID-19, the breadth of viral and vaccine cross-reactivity toward the ever-mutating Spike protein among variants of concern (VOCs) has not yet been compared between children and adults. We assessed antibodies to conformational Spike in COVID-19-naïve children and adults vaccinated by BNT162b2 and ChAdOx1, and naturally infected with SARS-CoV-2 Early Clade, Delta, and Omicron. Sera were analyzed against Spike including naturally occurring VOCs Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1, and variants of interest Epsilon, Kappa, Eta, D.2, and artificial mutant Spikes. There was no notable difference between breadth and longevity of antibody against VOCs in children and adults. Vaccinated individuals displayed similar immunoreactivity profiles across variants compared with naturally infected individuals. Delta-infected patients had an enhanced cross-reactivity toward Delta and earlier VOCs compared to patients infected by Early Clade SARS-CoV-2. Although Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1 antibody titers were generated after Omicron infection, cross-reactive binding against Omicron subvariants was reduced across all infection, immunization, and age groups. Some mutations, such as 498R and 501Y, epistatically combined to enhance cross-reactive binding, but could not fully compensate for antibody-evasive mutations within the Omicron subvariants tested. Our results reveal important molecular features central to the generation of high antibody titers and broad immunoreactivity that should be considered in future vaccine design and global serosurveillance in the context of limited vaccine boosters available to the pediatric population.

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http://hdl.handle.net/10453/176705